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Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinical

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… The use of appetite stimulants in addition to low-dose Dexa such as dronabinol, metoclopramide, and megestrol may improve appetite and cause modest weight gain. 3 , 24 One randomized controlled trial comparing dronabinol with megestrol reported megestrol to be superior compared to dronabinol both for … The study found no difference when dronabinol-megestrol combination was compared to megestrol alone. 25 In a study by Jakubowiak et al., 100% of patients (n=21) received prophylactic megestrol acetate (160–400 mg daily) and 5-HT3 antagonist but 29% (n=6) of patients remained anorexic and 5% (n=1) patients …

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.

BackgroundGlucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy.MethodsA systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO) and other resources were used. Data was extracted using a standar

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… The second trial is a comparison of prednisolone versus megestrol acetate; those in the megestrol acetate arm did significantly worse [ 10 ]. As mentioned in Table 12 , no radiation with a curative intent or chemotherapy was given in the second trial (F. Macbeth, personal communication). … A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic Cancer 1991 68 34 39 2049750 10.1002/1097-0142(19910701)68:1<34::AID-CNCR2820680107>3.0.CO;2-Q Patel SR Kvols LK Hahn RG Windschitl H Levitt R Therneau T A phase II randomized trial of megestrol acetate or dexamethasone …

Ontology-based collection, representation and analysis of drug-associated neuropathy adverse events.

BackgroundNeuropathy often occurs following drug treatment such as chemotherapy. Severe instances of neuropathy can result in cessation of life-saving chemotherapy treatment.ResultsTo support data representation and analysis of drug-associated neuropathy adverse events (AEs), we developed the Ontology of Drug Neuropathy Adverse Events (ODNAE). ODNAE extends the Ontology of Adverse Events (OAE). Our combinatorial approach identified 215 US FDA-licensed small molecule drugs that induce signs and symptoms of various types of neuropathy. ODNAE imports related drugs from the Drug Ontology (DrON) wi

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… , Dexamethasone, Fluticasone, Fluticasone propionate, antagonists 2: Bicalutamide, Megestrol modulators 3. … , Dexamethasone, Fluticasone, Fluticasone propionate, antagonists | 2: Bicalutamide, Megestrol modulators | 3. …

Efficacy and Effectiveness of Carnitine Supplementation for Cancer-Related Fatigue: A Systematic Literature Review and Meta-Analysis.

BackgroundCarnitine deficiency has been implicated as a potential pathway for cancer-related fatigue that could be treated with carnitine supplementation. The aim of this systematic literature review and meta-analysis was to evaluate the literature regarding the use of supplemental carnitine as a treatment for cancer-related fatigue.MethodsUsing the PRISMA guidelines, an electronic search of the Cochrane Library, MEDLINE, Embase, CINAHL and reference lists was conducted. Data were extracted and independently assessed for quality using the Academy of Nutrition and Dietetics evidence analysis by

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… Maccio et al. [ 25 ] reported that a combination therapy that included carnitine (as well as celecoxib, alpha lipoic acid, carboxycysteine and megestrol acetate) resulted in a significantly improved CRF compared to the control group. … Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/− megestrol acetate for patients with cancer-related anorexia/cachexia syndrome Clin. Nutr. 2012 31 176 182 10.1016/j.clnu.2011.10.005 22047681 31. Graziano F. Bisonni R. Catalano V. Silva R. Rovidati S. …

Does Therapeutic Repurposing in Cancer Meet the Expectations of Having Drugs at a Lower Price?

Therapeutic repurposing emerged as an alternative to the traditional drug discovery and development model (DDD) of new molecular entities (NMEs). It was anticipated that by being faster, safer, and cheaper, the development would result in lower-cost drugs. As defined in this work, a repurposed cancer drug is one approved by a health regulatory authority against a non-cancer indication that then gains new approval for cancer. With this definition, only three drugs are repurposed for cancer: Bacillus Calmette-Guerin (BCG) vaccine (superficial bladder cancer, thalidomide [multiple myeloma], and p

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… Megestrol acetate was also FDA-approved for endometrial cancer in 1971 [ 29 ]. The current FDA label of medroxyprogesterone indicates its use for pregnancy prevention and managing endometriosis-associated pain. … In contrast, megestrol acetate is indicated for treating anorexia, cachexia, or an unexplained significant weight loss in patients diagnosed with acquired immunodeficiency syndrome. …

Low-dose of olanzapine has ameliorating effects on cancer-related anorexia.

BACKGROUND: Olanzapine (OLZ) has become well-known for its antiemetic effects on chemotherapy-induced nausea and vomiting. However, it remains unclear whether OLZ also has efficacy for treating cancer-related anorexia. This study, therefore, retrospectively examined whether or not OLZ administration affects the food intake in anorexic cancer patients who exhibit neither nausea nor vomiting. METHODS: Eighty patients prescribed OLZ were extracted from 951 inpatients who consulted with our palliative care team at Chiba University Hospital from April 2008 to March 2016. Their food intake describe

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… As a matter of fact, one study suggested that combination treatment with OLZ and megestrol acetate has a beneficial effect on cancer-related anorexia, while one study reported that OLZ failed to increase the body weight of cancer cachexia patients. 15 , 16 Our current study was, therefore, performed … 10.1007/s00520-016-3101-x 14 Mackintosh D Olanzapine in the management of difficult to control nausea and vomiting in a palliative care population: a case series J Palliat Med 2016 19 1 87 90 26398872 10.1089/jpm.2015.0224 15 Navari RM Brenner MC Treatment of cancer-related anorexia with olanzapine and megestrol …

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients.

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are au

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… Garcia et al. [ 132 ] conducted a meta-analysis that included 23 RCTs from 3428 patients with different cancers to evaluate the safety and efficacy of the progesterone analogue Megestrol acetate (MA) on anorexia–cachexia syndrome. … A three-arm trial of megestrol acetate, dexamethasone, or fluoxymesterone conducted on 496 randomly selected advanced cancer patients documented that MA was more effective compared to fluoxymesterone with respect to improvements in appetite [ 133 ]. …

Efficacy and Safety of Thalidomide As a Pre-Medication of Chemotherapy-Induced Nausea and Vomiting (CINV) Following Highly Emetogenic Chemotherapy (HEC): A Systematic Review and Meta-Analysis.

BACKGROUND: In China, thalidomide (THD) has been used to prevent chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC); however, there is limited evidence on the efficacy and safety of THD in this setting. The aim of this study was to evaluate the efficacy, safety, and impact on quality of life (QoL) of THD on CINV following HEC. METHODS: Electronic databases were systematically searched for all randomized controlled trials (RCTs) in HEC using THD. The primary outcomes were complete response (CR) and no nausea, Secondary outcomes were the incidence of

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… THD combined with megestrol acetate was shown to be effective in terms of appetite, body weight, and QoL ( 44 ). This study has several strengths. Firstly, we included 34 RCTs and 3168 cases, expanding the scope and number of THD studies and greatly improving sample size and test efficacy. … Clinical Studies on the Treatment of Cancer Cachexia With Megestrol Acetate Plus Thalidomide . Chemotherapy ( 2012 ) 58 ( 6 ): 461–7 . doi: 10.1159/000346446 23406994 …

Sarcopenia in Older Adults with Hematologic Malignancies: A Comprehensive Review of Epidemiology, Prognosis, and Interventions.

Hematologic malignancies, including leukemias, lymphomas, and multiple myeloma, are diseases of older adults (age ≥ 60 years). Treatment decisions in older adults with cancer are heavily influenced by patient fitness: the ability of an individual patient to tolerate the off-target effects of anti-cancer therapy. Sarcopenia, defined as low muscle mass and strength, is increasingly recognized as an important marker of fitness. Furthermore, sarcopenia is known to be modifiable with nutrition and exercise interventions in older adults without cancer, but such evidence is limited for patients with

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… Agents impacting appetite include megestrol acetate [ 150 ], cannabinoids [ 151 ], growth differentiation factor 15 (GDF-15) antagonists (ponsegromab) [ 152 ], ghrelin mimetics (anamorelin) [ 153 ], and olanzapine [ 154 ]. …

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study.

CASE STUDY RS, a 36-year-old female, presented to the emergency department (ED) of a large academic medical center upon the advice of her pr … hen tablets 5-325 mg, two every 4 hours as needed for pain; prednisone 10 mg, one tablet daily; and megestrol 40 mg/mL suspension, 20 mL once daily for appetite stimulation. RS was admitted to an inpatient medical oncology service and evaluated by the oncology advanced practitioner (AP) on her second inpatient day. Upon exam, RS was nonverbal except for moa …

Antibodies to watch in 2013: Mid-year update.

The transitions of antibody therapeutics to late-stage clinical development, regulatory review and the market are proceeding at a rapid pace in 2013. Since late 2012, two monoclonal antibody (mAb) therapeutics (itolizumab, trastuzumab emtansine) received their first approvals, first marketing applications for three mAbs (vedolizumab, ramucirumab, obinutuzumab) were submitted to regulatory agencies, and five mAbs (brodalumab, MABp1, moxetumomab pasudotox, tildrakizumab, rilotumumab) entered their first Phase 3 studies. The current total of commercially-sponsored antibody therapeutics undergoing

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… The effects of MABp1 administered intravenously (IV) every two weeks, plus best supportive care will be compared with those of megestrol acetate administered daily plus best supportive care. The difference between the study arms in median overall survival from baseline to 18 mo will be compared. …

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncol

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… Breast Lapatinib Weak-mild inhibitor and substrate Moderate-strong inhibitor and substrate Inhibitor and substrate >99% Kidney, Liver, Thyroid Lenvatinib Weak inducer/weak inhibitor Substrate Substrate 98-99% Breast Letrozole Substrate No No 60% Brain Lomustine Mild inhibitor No No No Breast, Uterus Megestrol … and substrate | Moderate-strong inhibitor and substrate | Inhibitor and substrate | >99% Kidney, Liver, Thyroid | Lenvatinib | Weak inducer/weak inhibitor | Substrate | Substrate | 98-99% Breast | Letrozole | Substrate | No | No | 60% Brain | Lomustine | Mild inhibitor | No | No | No Breast, Uterus | Megestrol …

Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release.

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously in

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… Busquets S Serpe R Sirisi S Toledo M Coutinho J Martínez R Orpí M López-Soriano FJ Argilés JM Megestrol acetate: its impact on muscle protein metabolism supports its use in cancer cachexia Clin Nutr. 2010 29 6 733 737 10.1016/j.clnu.2010.06.003 20621398 33. … Argilés JM Anguera A Stemmler B A new look at an old drug for the treatment of cancer cachexia: megestrol acetate Clin Nutr. 2013 32 3 319 324 10.1016/j.clnu.2013.01.004 23395103 34. …

Pterostilbene in the Management and Treatment of Multiple Myeloma.

Multiple Myeloma is a malignancy of the plasma cells of the bone marrow. This cancer rapidly becomes refractory to many of the currently available chemotherapeutic regimens used against it, requiring an alternative option or supplementary therapy. Pterostilbene is a naturally occurring compound in a variety of commonly consumed plants that exhibits strong antioxidant properties and, lately, has shown increasing activity as an anti-neoplastic compound. A review of the literature published since 2015 on Google Scholar and PubMed was conducted, with a focus on randomized controlled trials and an

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… In a clinical trial (more details found in Appendix A ) with endometrial cancer patients, PT, when combined with Megestrol Acetate, suppressed a number of pro-tumorigenic and inflammatory pathways [ 26 ]. …

Keyword Index for Volume 105

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… lymphoma 586, 1402, 1414, 1684, 1768 M30 1830 malignant germ cell tumour 493 malignant melanoma 231, 1023 malignant mixed Mullerian tumours 897 mammography 1082, 1669 marker 673, 1726 matrix metalloproteinase-13 1615 maxillary sinus 833 Mcl-1 221 meat intake 1096 medical oncology 1166 megestrol …

Should oncologists trust cannabinoids?

Cannabis enjoyed a "golden age" as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians

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… The 469 patients enrolled were randomized to receive oral megestrol acetate, oral dronabinol or both and followed-up. The results, however, showed that megestrol acetate was superior to Dronabinol and that the combination of the two was not better than single drug megestrol therapy. …

Selinexor in acute myeloid leukemia: therapeutic applications and current challenges.

This article aims to review the current application status and research advancements of selinexor in the treatment of acute myeloid leukemia (AML). Selinexor, as the first oral selective inhibitor of nuclear export protein Exportin-1 (XPO1), inhibits the abnormal nuclear export of tumor suppressor proteins by blocking XPO1, thereby restoring their activity and exerting antitumor effects. Clinical studies have shown that selinexor monotherapy or combination therapy has demonstrated good anti-leukemia effects in AML, especially in patients with relapsed/refractory AML. In addition, the combinati

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… Gastrointestinal | Nausea | 53% | — | 5-HT3 antagonists, Neurokinin 1 receptor antagonists, Benzodiazepines, and Cannabinoid receptor antagonists, etc Vomiting | 38% | 5% Diarrhea | 39% | 3% | Loperamide and Bismuth Subsalicylate Systemic | Fatigue | 60% | 14% | Methylphenidate, etc Decreased appetite | 53% | — | Megestrol … Appetite stimulants: such as Megestrol, Cannabinoid drugs, or Olanzapine Considering the mechanism of action of selinexor, its inhibition of XPO1 affects the nucleocytoplasmic transport of various signaling pathways and proteins within the cell, which may partly explain the occurrence of the aforementioned …

Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer.

Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over … other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (po …